1. Field of the Invention
The present invention is a preventive or therapeutic agent for pollen allergy, allergic rhinitis, atopicdermatitis, asthma or urticaria or a health food for prevention, improvement or reduction of symptoms thereof.
2. Description of the Related Art
In recent years, there has been a rapid increase in the number(s) of patients suffering from allergies caused by cedar pollen and by plants such as Ambrosia artemisiifolia, Dactylis glomereta, Phleumpratanse, and birch or their pollen. In pollen allergies, chemical transmitters such as histamine and leukotriene and various enzymes are liberated from mast cells and basophils by pollen entering the body, and the typical symptoms of allergic conjunctivitis and allergic rhinitis (such as sniffles, stuffiness and sneezing) thereby appear, particularly in the nose and eyes.
There has been also an increase in allergic rhinitis, atopic dermatitis, asthma, urticaria, etc., caused not only by pollen, but also by house dust, ticks, etc., carrying allergens.
As a therapeutic countermeasure therefore, preventive therapy by anti-allergic agents has been carried out. This has consisted of a symptomatic treatment by new generation antihistaminic agents having fewer side effects on the nerves etc., orally administered agents such as various antagonists to chemical transmitters and inhibitors of the liberation of chemical transmitters, steroidal agents having a rapid pharmaceutical effect, and antihistaminic nasal drops having immediate effect and strong action, as well an hyposensitizing therapy: etc. However, traditional Chinese drugs or antiallergic agents having a satisfactory effect in preventive therapy have yet to be found. In addition, with regard to antihistaminic agents and steroidal preparations, which are used in symptomatic treatment, their side effects often cause problems. In terms of therapy, it has been also reported that the degree of patients"" satisfaction with the current status of treatment is extremely low. On the other hand, hyposensitizing therapy, while considered adequate by some, is beginning to show its limitations.
In U.S. Pat. No. 5,882,672, it is reported that when the seeds of one or more (preferably both) of the genera Cucurbita moschata and Plantago asistica, and the flowers of Lonicera japonica are added to feed, natural infections by parasites, bacteria and viral diseases are largely prevented, the prophylactic force of living bodies is enhanced, and the flesh and ooplasm are improved. A feed in which two kinds of crude drugs composed of seeds, those of Cucurbita moschata and Plantago asiatica, and two kinds of crude drugs composed of flowers, those of Lonicera japonica and Carthamus tinctorius, were combined, was given to chickens to improve the quality of their eggs. Moreover, better heath and survival rates, improvement in ooplasm and anti-leucocytozoonosis were observed. Further, in quail, the suppression of anti-Newcastle disease and enteric coccidium and a reduction in the incidence of the number of Staphylococci were also observed.
In U.S. Pat. No. 4,421,746, it is stated that an interferon inducer can be extracted from the plants of the genus Cucurbitaceae, such as Japanese pumpkin and, in U.S. Pat. No. 4,456,597, antiviral activity and anti-tumor activity of interferon inducers extracted from Carthamus tinctorius were also reported, leading to the conclusion that the inducer is useful as an anti-tumor agent and agent for the improvement of physiological action and general enhancement of health. In addition, in U.S. Pat. No. 4,469,685, it is reported that interferon inducers may be extracted from the flowers of Lonicera japonica, seeds of Plantago asiatica, etc., and are useful for the prevention of, and therapy, for viral infections in human beings and animals. In Japanese Patent Laid-Open No. 116,498/1999, a macrophage activator is described in which two crude drugsxe2x80x94seeds of Cucurbita moschata and flowers of Carthamus tinctoriusxe2x80x94are combined and, in Japanese Patent Laid-Open No. 281,584/2000, a neutrophil activator wherein four kinds of crude drugsxe2x80x94seeds of Cucurbita moschata, flowers of Carthamus tinctorius, seeds or total plant of Plantago asiatica, and flowers of Carthamus tinctorius and Lonicera japonicaxe2x80x94are combined, is described.
The present inventors have carried out an intensive investigation with the object of finding further specific uses of crude drugs such as the seeds of Cucurbita moschata and Plantago asiatica, and the flowers of Carthamus tinctorius and Lonicera japonica, etc., having such excellent effects as mentioned above. As a result, it has bean found that a combination of two kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and flowers of Carthamus tinctoriusxe2x80x94with at least one crude drug selected from Plantago asiatica, Lonicera japonica, Glyoyrrhiza uralensis, Coixlachryma-jobi var. ma-yuen, Zingiber officinale, Curcuma longa, Curcuma zedoaria, Artemisia argyi, etc., (particularly a combination of four crude drugsxe2x80x94seeds of Cucurbita moschata and Plantago asiatica, and flowers of Carthamus tinctorius and Lonicera japonicaxe2x80x94or a combination of Perilla frutescens var. crispa with a combination of three crude drugsxe2x80x94seeds of Cucurbita moschata, flowers of Carthamus tinctorius and cereal of Coix lachrymal-jobi var. ma-yuen), have had excellent effects in the prevention of, or therapy for pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria. In addition, it is also very safe.
Thus, the present invention is a preventive or therapeutic agent for pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria, containing two kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and flowers of Carthamus tinctoriusxe2x80x94and at least one crude drug selected from Plantago asiatica, Lonicera japonica, Glycyrrhiza uralensis, Coix lachrymal-jobi var. ma-yuen, Zingiber officinale, Curcuma longa, Curcuma zedoaria and Artemisia argyi, as effective components. The present invention is also a preventive or therapeutic agent for pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria, containing four kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and Plantago asistica, and flowers of Carthamus tinctorius and Lonicera japonicaxe2x80x94as effective components, or is a preventive or therapeutic agent for pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria, containing four kinds of crude drugsxe2x80x94seeds of Cucurbita moschata, flowers of Carthamus tinctorius, cereal of Coix lachrymal-jobi var. ma-yuen and leaves of Perillafrutescens var. crispaxe2x80x94as effective components.
Further, the present invention is a method for the prevention of, or therapy for, pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria by administration of two kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and flowers of Carthamus tinctoriusxe2x80x94and at least one crude drug selected from Plantago asiatica, Lonicera japonica, Glycyrrhiza uralensis, Coix lachrymal-jobi var. ma-yuen, Zingiber officinale, Curcuma longa, Curcuma zedoaria and Artemisia argyi, to patients. The present invention is also a method for the prevention of, or therapy for pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria by administration of four kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and Plantago asiatica, and flowers of Carthamus tinctorius and Lonicera japonicaxe2x80x94to patients or is a method for the prevention of or therapy for, pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria by the administration of four kinds of crude drugsxe2x80x94seeds of Cucurbita moschata, flowers of Carthamus tinctorius, cereal of Coix lachrymal-jobi var. ma-yuen and leaves of Perilla frutescens var. crispaxe2x80x94to patients.
Furthermore, the present invention is a method for the prevention of pollen allergy by the administration of two kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and flowers of Carthamus tinctoriusxe2x80x94and at least one crude drug selected from Plantago asiatica, Lonicera japonica, Glycyrrhiza uralensis, Coix lachyrmal-jobi var. ma-yuen, Zingiber officinale, Curcuma longa, Curcuma zedoaria and Artemisia argyi, to a person suffering every year from pollen allergy before the season for pollen allergy starts. The present invention is also a method for the prevention of pollen allergy by the administration of four kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and Plantago asiatica, and flowers of Carthamus tinctorius and Lonicera japonicaxe2x80x94to a person suffering every year from pollen allergy before the season for pollen allergy starts, or is a method for the prevention of pollen allergy by the administration of four kinds of crude drugsxe2x80x94seeds of Cucurbita moschata, flowers of Carthamus tinctorius, cereal of Coix lachrymal-jobi var. ma-yuen and leaves of Perilla frutescens var. crispaxe2x80x94to a person suffering every year from pollen allergy before the season for pollen allergy starts.
Still further, the present invention is a health food for the prevention or improvement or reduction of the symptoms of pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria containing two kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and flowers of Carthamus tinctoriusxe2x80x94and at least one crude drug selected from Plantago asiatica, Lonicera japonica, Glyoyrrhiza uralensis, Coix lachrymal-jobi var. ma-yuen, Zingiber officinale, Curcuma longa, Curcuma zedoaria and Artemisia argyi. The present invention is also a health food for the prevention or improvement or reduction of the symptoms of pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria containing four kinds or crude drugsxe2x80x94seeds of Cucurbita moschata and Plantago asiatica, and flowers of Carthamus tinctorius and Lonicera japonica, or is a health food for the prevention or improvement or reduction of the symptoms of pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria containing four kinds of crude drugsxe2x80x94seeds of Cucurbita moschata, flowers of Carthamus tinctorius, cereal of Coix lachrymal-jobi var. ma-yuen and leaves of Perilla frutescens var. crispa. 
Still furthermore, the present invention is a health food for the prevention of the onset of pollen allergy containing two kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and flowers of Carthamus tinctoriusxe2x80x94and at least one crude drug selected from Plantago asiatica, Lonicera japonica, Glycyrrhiza uralensis, Coix lachrymal-jobi var. ma-yuen, Zingiber officinale, Curcuma longa, Curcuma zedoaria and Artemisia argyi. The present invention is also a health food for the prevention of the onset of pollen allergy containing four kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and Plantago asiatica, and flowers of Carthamus tinctorius and Lonicera japonica, or is a health food for the prevention of the onset of pollen allergy containing four kinds of crude drugsxe2x80x94seeds of Cucurbita moschata, flowers of Carthamus tinctorius, cereal of Coix lachrymal-jobi var. ma-yuen and leaves of Perilla frutescens var. crispa. 
In the above-mentioned U.S. patents and literature, interferon inducing action, macrophage activating action, neutrophil activating action, inhibiting action against IgE antibody production, etc., for each of the crude drugs which are the effective components of the present invention have been reported, but there is neither disclosure nor suggestion at all concerning the preventive or therapeutic effects on specific human diseases.
The present inventors have confirmed that the combination of the crude drugs as combined in the present invention significantly reduces the symptoms of the diseases or prevents the onset of the symptoms of patients suffering from pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria. They have further confirmed that the combination of the crude drugs in the present invention is very safe and that, even after administration for as long as six years, no side effects have been found, and that it is suitable for common use not only as a therapeutic agent, but also as a preventive agent, functional food dietary supplement or health food for long term administration.
In addition, its joint use with conventional therapeutic agents does not seem to show any bad influence on the therapy. Its joint use with currently used therapeutic agents in an auxiliary manner is thought to be possible.
The present invention will now be discussed in more detail as hereunder.
First, the crude drugs used in the present invention will be described.
Seeds of Cucurbita moschata, the genus Cucurbitaceae and, in the present invention, seeds of similar plants achieving the object of the present invention, are included herein as well. Although the seeds of Cucurbita moschata may be used in their raw state, dry seeds are preferred because of their superior keeping qualities as medicament and health food. It is also possible to use the seed coat only. Components include cucurbitin, protein and vitamins A, B1, B2 and C, and carotene, etc.
Carthamus tinctorius is of the genus Compositae, and its dried tubular flower is used. Carthamin, safflor yellow, lignan and sterol are among its components. It is used for the therapy of circulation disorders such as female reproductive disorders, sensitivity to the cold, menopausal disorders, etc.
Plantago asiatica to a member of the Plantaginacea and its matured seeds (shazenshi) or entire plant (shazen) are used. They contain polysaccharides, plantenolic acid, succinic acid, adenine, aucubin, plantaginin, vitamins A and B1, etc. They are used an anti-inflammatory agents, diuretic agents and antidiarrheal agents in their crude forms.
Lonicera japonica is of the genus Gramineae and its flower or bud, leaf, stem or entire plant is used. It contains inositol, tannin, saponin, lonicerin, etc., as components. It is used as an antipyretic agent, poison antidote, diuretic agent, anti-inflammatory agent, etc., in its crude form.
Glyoyrrhiza uralensis is one of the Leguminosae and its dried root and rhizome are used. Its main medicinal component is glycyrrhizin. It is used as an alleviant, remitting agent, antitussive agent, analgesic agent and expectorant in its crude form.
Coix lachrymal-jobi var. ma-yuen is of the Gramineae and its cereal is used. It contains fatty oil as one of its components and in the oil coixenolide, coixol, amino acids, vitamin B1 and saccharide are contained. It is used as a cancer cell suppressor, antipyretic agent, sedative, tranquilizer and hypoglycemic agent in its crude form.
Zingiber officinale is one of the Zingiberaceae and its dried rhizome is used. As raw ginger, the same effect is possible, although dried ginger is preferred as a medicament and health food in view of its preservability. It contains essential oils and gingerol. It is used for improvement of blood circulation, hypertension, the excitation of vasomotor centers, and excitation of sympathetic nerves in its crude form.
Curcuma longa is of the genus Zingiberaceae, and its rhizome is used. It contains curoumin, and essential oils etc., among its components. It is used as a cholagogue, hypotensive agent, antibacterial agent, sedative, etc., in its crude form.
Curcuma zedoaria is of the Zingiberaceae and its rhizome is used. It contains curoumin, essential oils, etc., as the main components. It is used as an anti-tumor agent, antibacterial agent and stomachic agent in its crude form.
Artmesia argyi is a member of the Compositae and its dried leaves are used. It contains essential oils and vitamins A, B, C and D as the main components. It is used as an antibacterial agent, agent for stopping bleeding and shortening blood coagulation time, antitussive agent, expectorant, anti-inflammatory agent, appetite promoter, etc., in its crude form.
The therapeutic agent and the health food form of the present invention contains two kinds of crude drugsxe2x80x94seeds of Cucurbita moschata and flowers of Carthamus tinctoriusxe2x80x94and at least one crude drug selected from Plantago asiatica, Lonicera japonica, Glycyrrhiza uralensis, Coix lachrymal-jobi var. ma-yuen, Zingiber officinale, Curcuma longa, Curcuma zedoaria and Artemisia argyi as effective components; the particularly preferred form is a compound of four kinds of crude drugs, i.e., seeds of Cucurbita moschata and Plantago asiatica, and flowers of Carthamus tinctorius and Lonicera japonica. A combination of three kinds of crude drugsxe2x80x94seeds of Cucurbita moschata, flowers of Carthamus tinctorius and cereal of Coixlachryma-jobi var. ma-yuenxe2x80x94to which Perilla frutescens var. crispa is supplemented, is preferred as well.
In the present invention, these crude drugs may be used as crude powder or as an extract with water or organic solvents. Thus, they are used as crude powder, solvent preparation, powdery preparation, molded preparation, exudate, etc. With regard to the organic solvents, alcohol, acetone, etc., may be used and extraction may be accomplished using a mix of two or more kinds of organic solvents. In the extraction, several times as much solvent is added to the crude drug, and the extraction or extrusion is carried out at ambient temperature or with heating. The extracted essence of each crude drug may be extracted individually and then mixed or the essence may be extracted from pre-mixed fresh herbs. When a crude drug is used, it may be in its fresh/crude form, after drying in the shade, or after drying and then finely cutting or powdering.
The above-mentioned powder of crude drug or extract with water or with organic solvent may be utilized as health food, functional food or dietary supplement or medicament as it is, or after making into various forms by a method well known.
For example, medicament or functional food or dietary supplement maybe provided in the form of tablets, diluted powder, fine granules, capsules, pills or syrup for oral use by means of a conventional method of preparation. For making into preparations, it is possible to add fillers, binders, disintegrating agents, lubricants, buffers, corrigents, stabilizers, etc., thereto. At least one inert diluent such as lactose, mannitol, glucose, hydroxypropyl cellulose, finely crystalline cellulose, starch, polyvinylpyrrolidone or magnesium metasilicate aluminate is mixed therewith. In addition to the inert diluents, the composition may contain additives such as lubricants (e.g., magnesium stearate, starch and talc), disintegrating agents (e.g., calcium cellulose glycolate), stabilizers (e.g., lactose) and solubilizing aids (e.g., glutamic acid and aspartic acid) in accordance with conventional methods. Tablets or pills may be coated, if necessary, with a sugar cost such as sucrose, gelatin, agar, pectin, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, etc., or with the film of a substance which is soluble in the stomach or in the intestine.
To such an extent that the crude drug which is the effective component of the present invention is not affected, it is also possible to further combine it with caffeine, water-soluble vitamins such as vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, biotin, carnitine, pantothenic amid, nicotinic acid and derivatives thereof, fat-soluble vitamins such as vitamin A, vitamin E and derivatives thereof, and amino acids such as taurine and arginine. It is further possible that oriental herbs (such as licorice root, ginkgo, dandelion, chrysanthemum flower, carrot, cinnamon, etc.) or western herbs (such as Serenoa repens, Hypericum perforatum, echinacea, aniseed, annual chamomile (chamomile), rosemary, mint, eucalyptus, lavender, rose, hibiscus, aloe, etc.) may be added in a supplementary manner. It Is also preferred to combine the crude drug with Perilla frutescens var. crispa, which has been reported to be particularly effective for pollen allergy, allergic rhinitis and atopic dermatitis (FOOD Style, 21, 2(4), 50-54, 1998) in a (n) supplementary manner.
Liquid compositions for oral use contain a pharmaceutically acceptable emulsion, solution, suspension, syrup, elixir, etc., and contain a commonly used inert diluent such as pure water or ethanol. In addition to the inert diluent, the composition may also contain a moisturizer, an auxiliary agent such as a suspending agent, sweeteners, flavor agents, aromatic agents and antiseptic agents.
In the case of health food, it is possible to provide the compound in the form of a beverage or confection such as a jelly. biscuit, cookie, candy, etc.
The present invention consists of seeds of Cucurbita moschata, flowers of Carthamus tinctorius, and at least one kind of crude drug from the following: Plantago asiatica, Lonicera japonica, Glycyrrhiza uralensis, Coix lachrymal-jobi var. ma-yuen, Zingiber officinale, Curcuma longa, Curcuma zedoaria and Artemisia argyi, as effective ingredients. Moreover, it is more effective when this invention contains seeds of Cucurbita moschata in a percentage of from 20% to 60%, a percentage of flowers of Carthamus tinctorius from 10% to 40%, and each of the other crude drugs listed from 5% to 50%.
The combination of crude drugs according to the present invention may be appropriately determined for each case, taking age, gander, etc., of the subject into consideration. Usually, when 0.5-2 g or, preferably a total amount of 1 g of the crude drugs a day to a 60 kg adult is orally administered: the desired therapeutic or preventive effect can be achieved without any side effects.
The combination of crude drugs according to the present invention can be used not only as a preventive/therapeutic agent and health food for humans, but also as a therapeutic agent and health food for the improvement/reduction of health problems in pets such an dogs and cats.